Phenotypes of severe cutaneous adverse reactions caused by nonsteroidal anti-inflammatory drugs

Young Min Ye, Suh Young Lee, Young Hee Nam, Young Il Koh, Sae Hoon Kim, Sujeong Kim, Hye Ryun Kang, Min Hye Kim, Jun Gyu Lee, Jung Won Park, Hye Kyung Park, Hyen O. La, Mi Yeong Kim, Seong Ju Park, Yong Eun Kwon, Jae Woo Jung, Sang Hyon Kim, Cheol Woo Kim, Min Seok Yang, Min Gyu KangJin Yong Lee, Joo Hee Kim, Sang Heon Kim, Gyu Young Hur, Young Koo Jee, Hyun Jung Jin, Chan Sun Park, Yi Yeong Jeong

    Research output: Contribution to journalArticlepeer-review

    13 Citations (Scopus)


    Purpose: Nonsteroidal anti-inflammatory drugs (NSAIDs) are common cause of severe cutaneous adverse reactions (SCARs). The present study aimed to investigate the characteristics of SCARs induced by NSAIDs in the Korean SCAR registry. Methods: A retrospective survey of NSAID-induced SCARs recorded between 2010 and 2015 at 27 university hospitals in Korea was conducted. Clinical phenotypes of SCARs were classified into Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), SJS-TEN overlap syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS). Causative NSAIDs were classified into 7 groups according to their chemical properties: acetaminophen, and propionic, acetic, salicylic, fenamic and enolic acids. Results: A total of 170 SCARs, consisting of 85 SJS, 32 TEN, 17 SJS-TEN overlap syndrome and 36 DRESS reactions, were induced by NSAIDs: propionic acids (n=68), acetaminophen (n=38), acetic acids (n=23), salicylic acids (n=16), coxibs (n=8), fenamic acids (n=7), enolic acids (n=5) and unclassified (n=5). Acetic acids (22%) and coxibs (14%) accounted for higher portions of DRESS than other SCARs. The phenotypes of SCARs induced by both propionic and salicylic acids were similar (SJS, TEN and DRESS, in order). Acetaminophen was primarily associated with SJS (27%) and was less involved in TEN (10%). DRESS occurred more readily among subjects experiencing coxib-induced SCARs than other NSAID-induced SCARs (62.5% vs. 19.7%, P = 0.013). The mean time to symptom onset was longer in DRESS than in SJS or TEN (19.1 ± 4.1 vs. 6.8 ±1.5 vs. 12.1 ± 3.8 days). SCARs caused by propionic salicylic acids showed longer latency, whereas acetaminophen- and acetic acid-induced SCARs appeared within shorter intervals. Conclusions: The present study indicates that the phenotypes of SCARs may differ according to the chemical classifications of NSAIDs. To establish the mechanisms and incidences of NSAID-induced SCARs, further prospective studies are needed.

    Original languageEnglish
    Pages (from-to)212-221
    Number of pages10
    JournalAllergy, Asthma and Immunology Research
    Issue number2
    Publication statusPublished - 2019 Mar 1

    Bibliographical note

    Funding Information:
    This study was supported by a grant from the Ministry of Food and Drug Safety and the Korean Institute of Drug Safety and Risk Management for operation of the regional pharmacovigilance center in 2018 and a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI17C0970).

    Publisher Copyright:
    Copyright © 2019 The Korean Academy of Asthma, Allergy and Clinical Immunology • The Korean Academy of Pediatric Allergy and Respiratory Disease


    • Anti-inflammatory agents
    • Drug hypersensitivity
    • Non-steroidal
    • Stevens-johnson syndrome

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology
    • Pulmonary and Respiratory Medicine


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